Overview. As before, this Core consists of two components: A General Administrative Component, and a Mouse Management Component. The General Administrative Component works to maintain the cohesiveness of the whole program and its functions by organizing group meetings, retreats and journal clubs, and by dealing with any and all inter- Departmental or Institutional issues that arise. It also organizes internal and external reviews of the program, as well as making sure that renewal applications are submitted in a timely fashion. It regularly tracks the financial status of the program on a monthly basis, and assists in hiring and other personnel issues. In addition, the Core identifies newly published literature relevant to the program, and distributes to the appropriate investigators within the program. The goal of the administrative component is to make certain that the entire program functions as efficiently and optimally as possible. The Mouse Management Component supports 1 full time and one part-time animal technician. These individuals who are fully trained and engaged in the maintenance of gene-targeted and transgenic mouse models proposed in the individual projects. This component has the necessary equipment and space in a pathogen-free mouse-specific vivarium, as detailed below. The actual production of new mouse models will be done through the currently established UCSD Transgenic Mouse and Embryonic Stem Cell Gene Targeting Core, please see http://cancer.ucsd.edu/Research/Shared/tgm/default2.asp. This state-of-the-art facility was originally started with major support and advice from J. Marth (Project 1 leader) and has since developed an excellent track record in the production of genetically altered mice. Thus, rather than doing gene targeting ourselves, it now makes sense for this program to pay via fee-for-service for the generation of mice through this established UCSD Core. While the total costs are about the same, we avoid duplicative functions at the institution. Since our past experience with this approach has been good, we have decided to continue it in the current proposal. Budgetary Approach: Based on our experience to date, we also feel it is best to keep the daily management and breeding of mice, the animal technicians involved, the costs of mouse cage space, and the use of approaches such a Speed Congenics (see below) as a Core function - rather than allocating resources to each project for these activities. This approach also allows the maximum flexibility in accommodating the needs of all the projects, which will vary from year to year. While this makes for a rather large budget for an Administrative Core, most of the budget is actually for mouse-related costs. The administrative component budget remains very much the same as in the previous version of the grant.